Stabilized High Concentration Anti-Integrin alphavbeta3 Antibody Formulations

Abstract

The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to integrin αVβ3, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin αVβ3, which formulations are substantially free of surfactant, inorganic salts, and / or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating an inflammatory disorder, an autoimmune disorder, a disorder associated with aberrant expression and / or activity of integrin αVβ3, a disorder associated with abnormal bone metabolism, a disorder associated with aberrant angiogenesis or cancer utilizing the liquid formulations of the present invention.

Description

[0001]This application is entitled to and claims priority benefits to U.S. Provisional Application Ser. No. 60 / 443,777, filed Jan. 30, 2003, which is incorporated herein by reference in its entirety.1. INTRODUCTION[0002]The present invention relates to high concentration liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin αVβ3 which formulations exhibit stability, low to undetectable levels of antibody fragmentation, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention relates to liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin αVβ3, which formulations are substantially free of surfactant, inorganic salts or both. The present invention also relates to methods of preventing, treating, managing or ameliorating inflammatory diseases, auto...

AI Technical Summary

Benefits of technology

The present invention provides stable liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin αVβ3, which are suitable for preventing, treating, managing, and ameliorating symptoms associated with inflammatory and autoimmune diseases. These formulations are free of surfactant and inorganic salt, and they exhibit low to undetectable levels of antibody aggregation and fragmentation, as well as very little to no loss of the biological activities of the antibodies or antibody fragments during manufacture, preparation, transportation, and long periods of storage. These formulations enable quick administration of sterile dosages of antibodies without the need for accurate and sterile reconstitution of the antibodies prior to administration.

Problems solved by technology

Lyophilized formulations of antibodies have a number of limitations, including a prolonged process for lyophilization and resulting high cost for manufacturing.

Such reconstitution procedure is cumbersome and the time limitation after the reconstitution can cause a great inconvenience in administering the formulation to patients, leading to significant waste, if not reconstituted properly or if the reconstituted dose is not used within six (6) hours and must be discarded.

Prior liquid antibody preparations have short shelf lives and may lose biological activity of the antibodies resulting from chemical and physical instabilities during the storage.

Chemical instability may be caused by deamidation, racemization, hydrolysis, oxidation, beta elimination or disulfide exchange, and physical instability may be caused by antibody denaturation, aggregation, precipitation or adsorption.

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